title: Analysis of the Ush2a gene in medaka fish (Oryzias latipes).
abstract: Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP).
authors.affiliation: CIBER de Enfermedades Raras (CIBERER), Valencia, Spain ; Grupo de Investigación en Enfermedades Neurosensoriales, IIS-La Fe, Valencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Aller
authors.forename: Ana V
authors.initials: AV
authors.lastname: Sánchez-Sánchez
authors.forename: Javier U
authors.initials: JU
authors.lastname: Chicote
authors.forename: Gema
authors.initials: G
authors.lastname: García-García
authors.forename: Patricia
authors.initials: P
authors.lastname: Udaondo
authors.forename: Laura
authors.initials: L
authors.lastname: Cavallé
authors.forename: Marina
authors.initials: M
authors.lastname: Piquer-Gil
authors.forename: Antonio
authors.initials: A
authors.lastname: García-España
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Llopis
authors.forename: José M
authors.initials: JM
authors.lastname: Millán
authors.forename: José L
authors.initials: JL
authors.lastname: Mullor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D007758:Ear, Inner / Q000378:metabolism / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology; D009990:Oryzias / Q000196:embryology / Q000235:genetics*; D010641:Phenotype; D012160:Retina / Q000187:drug effects / Q000196:embryology; D013997:Time Factors
chemical_list: D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D060172:Morpholinos